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Background Postoperative acute kidney injury (PO-AKI) is a leading cause of short- and long-term morbidity and mortality, as well as progression to chronic kidney disease (CKD). The aim of this study was to explore the physicians’ attitude toward the use of perioperative serum creatinine (sCr) for the identification of patients at risk for PO-AKI and long-term CKD. We also evaluated the incidence and risk factors associated with PO-AKI and renal function deterioration in patients undergoing major surgery for malignant disease. Methods Adult oncological patients who underwent major abdominal surgery from November 2016 to February 2017 were considered for this single-centre, observational retrospective study. Routinely available sCr values were used to define AKI in the first three postoperative days. Long-term kidney dysfunction (LT-KDys) was defined as a reduction in the estimated glomerular filtration rate by more than 10 ml/min/m2 at 12 months postoperatively. A questionnaire was administered to 125 physicians caring for the enrolled patients to collect information on local attitudes regarding the use of sCr perioperatively and its relationship with PO-AKI. Results A total of 423 patients were observed. sCr was not available in 59 patients (13.9%); the remaining 364 (86.1%) had at least one sCr value measured to allow for detection of postoperative kidney impairment. Among these, PO-AKI was diagnosed in 8.2% of cases. Of the 334 patients who had a sCr result available at 12-month follow-up, 56 (16.8%) developed LT-KDys. Data on long-term kidney function were not available for 21% of patients. Interestingly, 33 of 423 patients (7.8%) did not have a sCr result available in the immediate postoperative period or long term. All the physicians who participated in the survey (83 out of 125) recognised that postoperative assessment of sCr is required after major oncological abdominal surgery, particularly in those patients at high risk for PO-AKI and LT-KDys. Conclusion PO-AKI after major surgery for malignant disease is common, but clinical practice of measuring sCr is variable. As a result, the exact incidence of PO-AKI and long-term renal prognosis are unclear, including in high-risk patients. Trial registration ClinicalTrials.gov, NCT04341974.

First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe, and the United States. COVID-19 is a new clinical syndrome, characterized by respiratory symptoms with varying degrees of severity, from mild upper respiratory illness to severe interstitial pneumonia and acute respiratory distress syndrome, aggravated by thrombosis in the pulmonary microcirculation. Three main phases of disease progression have been proposed for COVID-19: an early infection phase, a pulmonary phase, and a hyperinflammation phase. Although current understanding of COVID-19 treatment is mainly derived from small uncontrolled trials that are affected by a number of biases, strong background noise, and a litany of confounding factors, emerging awareness suggests that drugs currently used to treat COVID-19 (antiviral drugs, antimalarial drugs, immunomodulators, anticoagulants, and antibodies) should be evaluated in relation to the pathophysiology of disease progression. Drawing upon the dramatic experiences taking place in Italy and around the world, here we review the changes in the evolution of the disease and focus on current treatment uncertainties and promising new therapies.

Background The “END-of-Life ScorING-System” (ENDING-S) was previously developed to identify patients at high-risk of dying in the ICU and to facilitate a practical integration between palliative and intensive care. The aim of this study is to prospectively validate ENDING-S in a cohort of long-term critical care patients. Materials and methods Adult long-term ICU patients (with a length-of-stay> 4 days) were considered for this prospective multicenter observational study. ENDING-S and SOFA score were calculated daily and evaluated against the patient’s ICU outcome. The predictive properties were evaluated through a receiver operating characteristic (ROC) analysis. Results Two hundred twenty patients were enrolled for this study. Among these, 21.46% died during the ICU stay. ENDING-S correctly predicted the ICU outcome in 71.4% of patients. Sensitivity, specificity, positive and negative predictive values associated with the previously identified ENDING-S cut-off of 11.5 were 68.1, 72.3, 60 and 89.3%, respectively. ROC-AUC for outcome prediction was 0.79 for ENDING-S and 0.88 for SOFA in this cohort. Conclusions ENDING-S, while not as accurately as in the pilot study, demonstrated acceptable discrimination properties in identifying long-term ICU patients at very high-risk of dying. ENDING-S may be a useful tool aimed at facilitating a practical integration between palliative, end-of-life and intensive care. Trial registration Clinicaltrials.gov Identifier: NCT02875912; First registration August 4, 2016.

Objectives:To assess the feasibility and efficacy of implementing “Family Care Rituals” as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members.Design:Prospective, before-and-a

Background: International data on the epidemiology, ventilation practice, and outcomes in patients undergoing abdominal robotic-assisted surgery (RAS) are lacking. The aim of the study was to assess the incidence of postoperative pulmonary complications (PPCs), and to describe ventilator management after abdominal RAS. Methods: This was an international, multicentre, prospective study in 34 centres in nine countries. Patients ≥18 yr of age undergoing abdominal RAS were enrolled between April 2017 and March 2019. The Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score was used to stratify for higher risk of PPCs (≥26). The primary outcome was the incidence of PPCs. Secondary endpoints included the preoperative risk for PPCs and ventilator management. Results: Of 1167 subjects screened, 905 abdominal RAS patients were included. Overall, 590 (65.2%) patients were at increased risk for PPCs. Meanwhile, 172 (19%) patients sustained PPCs, which occurred more frequently in 132 (22.4%) patients at increased risk, compared with 40 (12.7%) patients at lower risk of PPCs (absolute risk difference: 12.2% [95% confidence intervals (CI), 6.8–17.6%]; P

Background Chronic pain after breast surgery (CPBS) has a disabling impact on postoperative health status. Mainly because of the lack of a clear definition, inconsistency does exist in the literature concerning both the actual incidence and the risk factors associated to CPBS. The aim of this prospective, observational study is to describe the incidence of and risk factors for CPBS, according to the definition provided by the IASP taskforce. The impact of CPBS on patients’ function and quality of life is also described. Methods Women aged 18+ undergoing oncological or reconstructive breast surgery from Jan until Apr 2018 at the Breast Unit of Careggi Hospital (Florence, Italy) were prospectively observed. Postoperative pain was measured at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 3 months (CPBS) after surgery. Preoperative, intraoperative, and postoperative factors were compared in CPBS and No-CPBS groups through multivariate logistic regression analysis. Results Among the 307 patients considered in this study, the incidence of CPBS was 28% [95% CI 23.1–33.4%]. Results from the logistic regression analysis suggest that axillary surgery (OR [95% CI], 2.99 [1.13–7.87], p = 0.03), preoperative use of pain medications (OR [95% CI], 2.04 [1.20–3.46], p = 0.01), and higher dynamic NRS values at 6 h postoperatively (OR [95% CI], 1.28 [1.05–1.55], p = 0.01) were all independent predictors for CPBS. Conclusions Chronic pain after breast surgery is a frequent complication. In our cohort, long-term use of analgesics for pre-existing chronic pain, axillary surgery, and higher dynamic NRS values at 6 h postoperatively were all factors associated with increased risk of developing CPBS. The possibility to early detect persistent pain, particularly in those patients at high risk for CPBS, might help physicians to more effectively prevent pain chronicisation. Trial registration ClinicalTrials.gov registration NCT04309929.

A maladaptive response to surgical stress might lead to postoperative complications. A multidisciplinary approach aimed at controlling the surgical stress response may reduce procedural complications and improve patients’ quality of life in the short and long term. Several studies suggest that psychological interventions may interact with the pathophysiology of surgical stress response, potentially influencing wound repair, innate and adaptive immunity, inflammation, perception of pain, and patients’ mood. The aim of this systematic review is to summarise the effects of perioperative psychological interventions on surgical pain and/or anxiety in adult patients scheduled for elective general abdominal and/or urologic surgery.We conducted a systematic review of controlled clinical trials and observational studies involving psychological interventions for adult patients scheduled for elective general abdominal and/or urologic surgery. Only studies reporting pain and/or anxiety among outcome measures were included in the systematic review. The following psychological interventions were considered: (1) relaxation techniques, (2) cognitive-behavioural therapies, (3) mindfulness, (4) narrative medicine, (5) hypnosis and (6) coping strategies.We examined 2174 papers. Among these, 9 studies were considered eligible for inclusion in this systematic review (1126 patients cumulatively): 8 are randomised controlled trials and 1 is an observational prospective pre/post study.Psychological characteristics widely influence the pathophysiological mechanisms underlying the neuroendocrine and inflammatory response to surgical stress, potentially interfering with surgical outcomes. Psychological interventions are technically feasible and realistically applicable perioperatively during abdominal and/or urologic surgery; they influence the pathophysiological mechanisms underlying maladaptive surgical stress response and might have positive effects on patients’ surgical outcomes, such as pain and anxiety.

Background: In a previous trial, in-line filtration significantly prevented postoperative phlebitis associated with short peripheral venous cannulation. This study aims to describe the cost-effectiveness of in-line filtration in reducing phlebitis and examine patients’ perception of in-hospital vascular access management with and without in-line filtration. Methods: We analysed costs associated with in-line filtration: these data were prospectively recorded during the previous trial. Furthermore, we performed a follow-up for all the 268 patients enrolled in this trial. Among these, 213 patients responded and completed 6 months after hospital discharge questionnaires evaluating the perception of and satisfaction with the management of their vascular access. Results: In-line filtration group required 95.60€ more than the no-filtration group (a mean of € 0.71/patient). In terms of satisfaction with the perioperative management of their short peripheral venous cannulation, 110 (82%) and 103 (76.9%) patients, respectively, for in-line filtration and control group, completed this survey. Within in-line filtration group, 97.3% of patients were satisfied/strongly satisfied; if compared with previous experiences on short peripheral venous cannulation, 11% of them recognised in-line filtration as a relevant causative factor in determining their satisfaction. Among patients within the control group, 93.2% were satisfied/strongly satisfied, although up to 30% of them had experienced postoperative phlebitis. At the qualitative interview, they recognised no difference than previous experiences on short peripheral venous cannulation, and mentioned postoperative phlebitis as a common event that ‘normally occurs’ during a hospital stay. Conclusion: In-line filtration is cost-effective in preventing postoperative phlebitis, and it seems to contribute to increasing patient satisfaction and reducing short peripheral venous cannulation–related discomfort

OBJECTIVES The aim of this prospective observational study was to evaluate the influence of OPRM1 polymorphism on the analgesic efficacy (including visual analog scale [VAS] scores and requirement for rescue analgesia) of a standard dose of intrathecal morphine. MATERIALS AND METHODS An Italian cohort of 63 parturients, scheduled for elective cesarean section at a tertiary University Hospital, received spinal anesthesia with hyperbaric bupivacaine and morphine 100 mcg. For the first 48 hours in the postoperative period the patients received acetaminophen 1 g IV q6hr. Incident pain was treated with ketorolac 30 mg IV. Every 6 hours the following parameters were registered: VAS at rest, VAS during movements, postoperative nausea and vomiting, pruritus, and rescue analgesic medications requirements. Age and anthropometric data, number of pregnancies, educational level, OPRM1 genotype, were also obtained. RESULTS Of the 63 patients enrolled, 45 (71%) were homozygous genotype A/A (118A group), whereas 18 carried the G variants of OPRM1 (A/G or G/G) (118G group). No significant differences in analgesic rescue doses' administration and in incidence of moderate/severe postoperative pain (VAS>3) between the 2 groups were observed. Pruritus was more frequent in the 118A group than in the 118G group in the first 24 hours of the postoperative period. DISCUSSION In the Italian population participating in this study there was a different incidence of pruritus in the postcesarean period in response to intrathecal opioids related to OPRM1 gene polymorphism, but not of postoperative pain.

BACKGROUND The control of postoperative pain (POP) is a key component of perioperative care. POP after vitreo-retinal surgery (VRS) has been under-investigated, and its incidence remains elusive. METHODS In order to assess POP after VRS, the associated risk factors and efficacy of the analgesic protocol in use at our institution, we made a one-year retrospective study on patients undergoing VRS. Patients aged >18 years, ASA Class I-III undergoing VRS entered the study. POP was evaluated by measuring a Numerical Rating Scale (NRS), and analgesic consumption. RESULTS A total of 782 patients entered the study. Patients received locoregional (LRA) or general anesthesia (GA) with supplemental block. Twenty-two percent of patients needed analgesics (acetaminophen in 97% of cases), mostly between two and six hours after surgery. The univariate analysis showed a positive association between POP and duration of surgery (P

Background: Technical factors at the moment of catheter insertion might have a role in peripherally inserted central catheter–related thrombotic risk. We performed a systematic review and meta-analysis to define the actual rate of peripherally inserted central catheter–related symptomatic deep vein thrombosis in patients in whom catheter insertion was performed according to ultrasound guidance, appropriate catheter size choice, and proper verification of tip location. Methods: We searched Medline, Embase, and Cochrane Library. Only prospective observational studies published in peer-reviewed journals after 2010 up to November 2018 reporting peripherally inserted central catheter–related deep vein thrombosis rate were included. All studies were of adult patients who underwent peripherally inserted central catheter insertion. Results were restricted to those studies which included in their methods ultrasound guidance for venipuncture, catheter tip location, and a catheter size selection strategy. Random-effect meta-analyses and arcsine transformation for binomial data were performed to pool deep vein thrombosis weighted frequencies. Results: Of the 1441 studies identified, 15 studies involving 5420 patients and 5914 peripherally inserted central catheters fulfilled our inclusion criteria. The weighted frequency of peripherally inserted central catheter–related deep vein thrombosis was 2.4% (95% confidence interval = 1.5–3.3) and remained low in oncologic patients (2.2%, 95% confidence interval = 0.6–3.9). Thrombotic rate was higher in onco-hematologic patients (5.9%, 95% confidence interval = 1.2–10). Considerable heterogeneity (I2 = 74.9) was observed and all studies were considered at high risk of attrition bias. Conclusions: A proper technique is crucial at the moment of peripherally inserted central catheter insertion. Peripherally inserted central catheter–related deep vein thrombosis rate appears to be low when evidence-based technical factors are taken into consideration during the insertion procedure.

Worldwide, the widespread use of extracorporeal blood purification therapies (EBPTs) is progressively increasing in everyday clinical practice, particularly in critical care settings. The efficacy of EBPTs on removal of inflammatory mediators is already well established in the literature. Nonetheless, clinical research is particularly cumbersome in this setting, and many clinical trials aiming at exploring the effect of EBPTs on outcomes have failed in demonstrating consistent results regarding 28-day- or hospital-mortality rates. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of EBPTs. The philosophy behind this Italian Registry is a renewal of the concept of “clinical research” in the field of EBPTs applied to critically ill, septic patients with or without acute kidney injury. The platform used for the registry – specifically designed for research purposes and fed by clinical data prospectively observed – promotes good practice with a positive and active interaction with the physician/researcher. This interaction has favorable real-time effects for the specific patient, providing “bed-side clinical feedbacks,” similarly to the decision support system. Examples of these issues are bundles reminders, suggestions for drug adjustment according to the extracorporeal clearance, clinical calculator for body mass index, or mechanical ventilation setting. The platform-physician interaction has additional useful effects on the single utilizing center, providing “mid-term, center-specific clinical feedbacks.” These generally consist of clusters of data taken over a certain period, for example, regarding patients’ outcome, microbiological data, or use of disposable for EBPTs.

Prone positioning (PP) is necessary for surgical access during posterior spine procedure. However, physiological changes occur in the PP. Typical findings are a decrease in arterial blood pressure and in cardiac output that could potentially lead to an alteration in cerebral perfusion. Therefore, we decided to study cerebral blood flow velocity (CBFV) with transcranial Doppler ultrasonography to evaluate the effect of the PP on cerebral hemodynamics.Twenty-two patients undergoing spine surgery in the PP were studied. General anesthesia was induced using 250 μg of fentanyl, 2 mg/kg of propofol, and 0.1 mg/kg of vecuronium, and was maintained with 0.25%-0.5% isoflurane, 50% nitrous oxide in oxygen, continuous infusion of 100 μg/kg/min of propofol, 1.5 μg/kg/h of fentanyl, and 0.15 mg/kg/h of ketamine. Continuous invasive arterial blood pressure, heart rate, electrocardiogram, and end-tidal carbon dioxide were monitored. CBFV with transcranial Doppler in the middle cerebral artery was first measured with the patients under general anesthesia in the supine position. Patients were then placed in the PP and remained in this position throughout surgery. CBFV, end-tidal carbon dioxide, heart rate, and blood pressure were measured continuously for 75 minutes after initiation of PP. This coincided with surgical exposure and minimal blood loss. Data were analyzed every 15 minutes for statistical significant change over time.Mean arterial blood pressure decreased 15 minutes after the installation of the PP and onward, but this decrease was not statistically significant. CBFVsyst (the maximal CBFV during the systolic phase of a cardiac cycle) and CBFVmean (the time averaged value of the maximal velocity envelope over 1 cardiac cycle) did not vary at any time points. CBFVdiast (the CBFV just before the acceleration phase [systole] of the next waveform) was lower at T3 (30 minutes after PP) compared to T1 (value derived averaging the first measure in the PP with the ones at 5 and 10 minutes) (P = .01), and the pulsatility index was higher at T5 (60 minutes after PP) compared to T0 (baseline, patient supine under general anesthesia) (P = .04). Data were analyzed at specific time points (T0 and T1). This value was derived by computing an average of the CBFV values collected at the first measure in the PP and at 5 and 10 minutes thereafter: T2, 15 minutes after PP; T3, 30 minutes after PP; T4, 45 minutes after PP; T5, 60 minutes after PP; and T6, 75 minutes after PP.Our data on CBFV during PP for spine surgery demonstrate preservation of cerebral perfusion during stable systemic hemodynamic conditions. The present results do not allow us to determine whether the PP would be similarly tolerated with increasing length of surgery, variations in systemic hemodynamics, and in different patient populations.

Continuous venovenous haemodialysis with high cut-off membrane (HCO-CVVHD) is often used in critically ill septic patients with acute kidney injury (AKI) to sustain renal function and to remove circulating inflammatory mediators. The aim of this study was to analyse the extracorporeal removal of linezolid and related alterations in pharmacokinetic/pharmacodynamic (PK/PD) parameters during HCO-CVVHD. Three critically ill septic patients with AKI, treated with linezolid and HCO-CVVHD, were prospectively observed. To calculate the extracorporeal clearance of linezolid and the PK parameters, effluent, pre-filter and post-filter samples were contemporaneously collected before linezolid infusion, just after 1-h infusion (maximum serum concentration; C(max)), at 3 h and 6 h after dosing, and before the next dose (trough serum concentration; C(min)). Linezolid C(max) and C(min) (pre-filter) ranged from 10.4-23.5 mg/L and from 2.9-10.3 mg/L. The dialysate saturation coefficient was 0.66-0.85 and the extracorporeal clearance with a diffusive dose of 35 m L/kg/h ranged from 2.1-2.5 L/h. Total linezolid clearance was between 1.7 L/h and 6.3 L/h. The total area under the plasma concentration-time curve (AUC0-∞) ranged from 95.1 mgh/L to 352.9 mgh/L, in accordance with the different clinical conditions. AUCfree/MIC ratios were always

A new light has recently been shed on palliative care, especially, on its multidisciplinary approach developed to improve the Quality of life of seriously ill patients and their families. However, palliative care is still often mistakenly referred to as an end-of-life care and wrongly interchanged with hospice care. Nephropathic patients usually present a decrease in expectancy and Quality of life and may benefit from palliative care as opposed to hospice care. Palliative care requires a tight collaboration among different health care professionals, patients and their families, to share diagnosis, prognosis, realistic goals of treatment and therapeutic decisions. Several approaches may be attempted to improve the Quality of life of chronic nephropathic patients, such as palliative dialysis, conservative management and peritoneal dialysis. For example, personalized goals and a wider concept of adequacy of extracorporeal treatment are the bases of palliative dialysis. In specific subgroups of frail patients, the pharmacological conservative management could be more appropriate than extracorporeal treatment, as the former reduces the burdens derived from invasive procedures. Finally, peritoneal dialysis could be an important option for frail patients to avoid an aggressive extracorporeal treatment while maintaining a gentle solute and fluid control. However, only limited evidences are available on palliative and hospice care performed on patients with Acute Kidney Injury (AKI). Herein, the main variables affecting the medical decision-making on palliative care in nephropathic patients are described, and the different approaches available to improve quality of palliative care during Chronic and Acute Kidney Injury are analyzed.

Trauma, surgery, and infection represent a common source of stress in critically ill patients admitted in intensive care units (ICUs). Although the consequences of stress response in critical illness are still debated and not well understood, many neural and hormonal responses have been recognized to activate homeostatic mechanisms aimed at favoring survival and healing. These responses develop toward three different phases: the first immediate and short (24 h) phase, termed ebb, is directed to immediate survival; the second longer phase (6–7 days), termed flow, is characterized by an increase in total body oxygen consumption and carbon dioxide production with hypermetabolism; the third phase, termed chronic, may last some months and identifies the post-stress period of critical illness. Although the effects of sedatives (analgesics and hypnotics) on tissue metabolic demand of critically ill patient remain difficult to be adequately defined, these drugs commonly delivered in intensive care units actually influence the stress response by decreasing neurohumoral reactions, involving the sympathetic system, and affecting the inflammatory mechanisms. After the neuroendocrine activation, uncontrolled metabolic reactions, characterized by catabolism and the resistance to anabolic signals as insulin, develop. Secondary negative effects (infections, muscle atrophy and weakness, respiratory insufficiency, delayed wound healing) can occur as direct consequences of metabolic phenomena that are clearly difficult to monitor. Finally, sedatives administered to control stress response clearly have detrimental effects (hemodynamic alterations, immunosuppression, delirium) that should be carefully evaluated in the context of a balance between benefits and damages.

Sleep is a complex process related to biologic and environmental factors essential to maintaining physiological and emotional well-being. Sleep disturbances and deprivation, and abnormal sleep architecture (prolonged sleep latency, sleep fragmentation, continuous arousals, a preponderance of inefficient sleep stages), frequently occur in critically ill patients, leading to adverse outcomes. Survivors of critical illness frequently refer to sleep deprivation as a major stressor associated with their admission. The following environmental (clinical and nonclinical) factors contribute to sleep disturbances in these patients: mechanical ventilation, drainage positioning and maintenance, bronchial aspiration, hygiene, nursing care, pain, light, and noise. Sleep duration in critically ill patients is shortened and fragmented, and sleep is essential for restoring energy and equilibrating the mind. Sleep deprivation hence alters cognition, leading to apathy, confusion, and delirium, all of which may increase morbidity and mortality. Sedatives are commonly given to critically ill patients to promote sleep, although physiological sleep and sedation may be significantly different. While patients may achieve an acceptable amount of sleep over a 24-h period, this sleep is both discontinuous and abnormally structured. Clinical guidelines strongly support and recommend the application of a multimodal approach aimed at promoting sleep that includes both environmental regulations and clinical assistance.

Critically ill patients often require sedative and analgesic drugs to optimize patient comfort, facilitate patient-ventilator synchrony, and allow tolerance to procedures. The level of sedation can change during a patient’s stay and an optimal degree of sedation is necessary to avoid the risk of oversedation and to reduce the risk of delirium, the length of mechanical ventilation, and the length of stay in the ICU.

Near-infrared spectroscopy (NIRS) has been used to detect in vivo microvascular alterations by means of a vascular occlusion test. We sought to analyse by NIRS the microcirculatory profile of patients undergoing prolonged tourniquet-induced bloodless condition for extremity surgery, and compare the results with time of ischemia and comorbidities. We conducted a prospective observational study on 42 patients undergoing upper limb surgery. Regional anaesthesia was achieved and ischemia was induced by a tourniquet cuffed at 250 mmHg. The probe of a NIRS monitor (InSpectra 325, Hutchiston, USA) was placed on the brachial muscle, and muscle oxygen saturation (StO2) was recorded continuously before anaesthesia, during and after surgery. The following variables were recorded: baseline StO2, StO2 desaturation slope during occlusion (dSlope, units/s), resaturation rate following ischemia (RR, units/s), hyperaemic peak (peak, units), and duration of the hyperaemic period following ischemia (hyperaemic time, s). Values of dSlope were similar among all patients. RR and hyperaemic time were significantly correlated with the duration of ischemia, but not with comorbidities [p = 0.007 CI (−35.64 to −13.1), and p

Background Continuous veno-venous hemodialysis with high cut-off membranes (HCO-CVVHD) removes inflammatory mediators involved in organ dysfunction during sepsis. The aim of the present study was to assess the variations in SOFA score and identify early predictors of short-term mortality in a cohort of patients with septic shock, treated with HCO-CVVHD for acute kidney injury (AKI). Methods An observational prospective multicenter cohort study was conducted in four mixed medical-surgical ICUs. Thirty-eight patients with septic shock and AKI (KDIGO stage≥1) treated with HCO-CVVHD have been included in this study. Patients were divided into Survivors and non-Survivors according to mortality observed at 72nd hr of treatment. The variation of SOFA scores and clinical/biochemical parameters were described over time for the entire population and specifically for Survivors and non-Survivors. Similarly, circulating inflammatory mediators (as IL-6, TNF-a and IL-10) were described over time. A logistic regression analysis was used to identify the baseline clinical and biochemical parameters associated with 72 hrs-ICU mortality. Results Overall, the mean SOFA score was 12±3 at baseline, 10.9±3 at 6hrs, 9.8±3 at 12hrs, 8.9±3.3 at 24 hrs, and 8±3.5 at 48 hrs after HCO-CVVHD initiation; and 6.5±2.7 at 24 hrs and 6.6±3 at 48 hrs after HCO-CVVHD discontinuation. In the multivariate regression analysis, baseline serum lactate levels and AKI stage independently correlated with short-term mortality during HCO-CVVHD. A significant reduction was observed in circulating levels of TNFα and IL-6 among Survivors. Conclusions SOFA score significantly decreased early after initiation of HCO-CVVHD in patients with septic AKI. Baseline lactate levels and the AKI stage resulted to be associated to 72 hrs-ICU-mortality.

Summary Organ dysfunction is common in ICU, and it is associated with high mortality rates, particularly among septic or complicated surgical patients. Scoring systems for organ dysfunction have a fourfold purpose: quantifying the entity and severity of organ dysfunction, stratifying and comparing patients as to morbidity and risk of mortality, tracking progression of critical illness in ICU and identifying patients who are unresponsive to therapies. The degree of organ dysfunction is strongly correlated with outcome, though in general the performance of organ dysfunction scores in terms of outcome prediction is inferior to that of classical severity scores, such as the Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II. Scoring systems for organ dysfunction can be divided into multiple organ dysfunction and single organ failure scores. The aim of this review is to summarize and compare the most commonly used organ dysfunction scores.

Summary Biomarkers are quantifiable indicators of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention. They have been recently introduced into clinical practice as a means for risk assessment, screening, diagnosis, staging, and prognosis. Some of them (cardiac and kidney biomarkers) have already found a precise role as the leading actor and actress in clinical medicine while others (pulmonary biomarkers) are still under evaluation in the different settings. Together with their invaluable properties, biomarkers have some important characteristics that should never be underestimated. A single biomarker rarely seems to have all the characteristics required to meet the clinical needs for a complete organ failure assessment, every biomarker seems to show different behaviour in different kinds of diseases, and several confounding factors have to be considered when interpreting biomarkers used for clinical assessment. The research on biomarkers is running fast and it is likely that a panel of biomarkers may be the best approach for achieving a complete patient assessment together with an adequate clinical evaluation and monitoring.

Background: Hemodialysis with high cut-off continuous veno-venous hemodialyzer (HCO-CVVHD) removes mediators of organ dysfunction during sepsis. This study assessed the clinical effects of HCO-CVVHD as compared to high-flux (HF) membranes during gram-negative sepsis. Methods: Intensive care unit (ICU), septic patients treated with HCO-CVVHD or HF-CVVHDF for AKI were retrospectively observed (January 2013-December 2014). Mechanical ventilation, vasopressors' requirements, ICU length of stay (LOS) and ICU in-hospital mortality were compared between groups. Results: Sixteen HCO and 8 HF patients were observed. Isolated pathogens included Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa. Median ratios of days-on-vasopressors and days-on-mechanical ventilation/ICU-LOS were 0.5, 1 and 0.8, 1 for HCO and HF groups (p < 0.03), respectively. ICU-LOS was 16 and 9 days (HCO- and HF-group, p = 0.03). ICU mortality rates were 37.5 and 87.5% for HCO and HF groups, respectively (p = 0.03). No statistical difference was found in in-hospital morality. Conclusion: Patients in HCO-CVVHD group spent lesser number of days on vasopressors and mechanical ventilation as a ratio to total ICU-LOS. In the same group, a reduction in ICU mortality was observed.

Background The benefits of an Acute Pain Service (APS) for pain management have been widely reported, but its diffusion is still limited. There are two APS models: anesthesiologist-based and a nurse-based model. Here we describe the development of a different APS model managed by anesthesia residents, and we report the first year of activity in a tertiary Italian university hospital (Careggi University Hospital, Florence, IT). Methods Patients were included in the APS were those undergoing abdominal and urologic surgery causing moderate or severe postsurgical pain. The service was provided for patients, beginning upon their exit from the operating room, for 4, 12, 24 and 48 h for iv, and up to 72 h for epidural therapy. Vital signs, static/dynamic VAS, presence of nausea/vomiting, sedation level, and Bromage scale in case of epidural catheter, were monitored. Results From September 2013 to April 2015, a total of 1054 patients who underwent major surgery were included in the APS: 542 from abdominal surgery and 512 from urological surgery. PCA and epidural analgesia were more adopted in general surgical patients than in urology (48 % vs 36 % and 15 % vs 2 %, respectively; P

Purpose Acute kidney injury (AKI) is a frequent complication in high-risk patients undergoing major surgery and is associated with longer hospital stay, increased risk for nosocomial infection and significantly higher costs. Materials and methods A prospective observational study exploring the incidence of AKI (AKIN classification at any stage) in high-risk patients within 48 hours after major abdominal surgery was conducted. Patients' preoperative characteristics, intraoperative management, and outcome were evaluated for associations with AKI using a logistic regression model. Results Data from 258 patients were analyzed. Thirty-one patients (12%) developed AKI, reaching the AKIN stage 1. No patient reached an AKIN stage higher than 1. AKI patients were older (75.2 vs 70.2 years; P=0.0113) and had a higher body mass index (26.5 vs 25.1 kg/m 2 ). In addition, AKI patients had a significantly longer ICU length of stay (3.4 vs 2.4 days; P = .0017). Creatinine levels of AKI patients increased significantly compared to the preoperative levels at 24 ( P = .0486), 48 ( P = .0011) and 72 hours ( P = .0055), while after 72 hours it showed a downwards trend. At ICU discharge, 28 out of 31 patients (90.3%) recovered preoperative levels. Multivariate analysis identified age (OR 1.088; P = .002) and BMI (OR 1.124; P = .022) as risk factors for AKI development. Moreover, AKI development was an independent risk factor for ICU stays longer than 48 hours (OR 2.561; P = .019). Conclusions Mild AKI is a not rare complication in high-risk patients undergoing major abdominal surgery. Although in almost the totality of cases, the indicators of renal function recovered to preoperative levels, post-operative AKI represents a primary risk factor for a prolonged ICU stay.

In patients with severe acute pancreatitis (SAP) early and persistent elevated circulating levels of interleukins (IL)-1, 2 and 6 and tumor necrosis factor (TNF)-α are linked to severity of disease and early multiple organ failure (MOF), while persistently elevated serum IL-10 is linked to immune paralysis and infectious complications. Although experimental and clinical evidence exists that continuous venovenous hemodiafiltration with high cutoff membranes (HCO-CVVHDF) efficiently removes inflammatory mediators from blood of patients with severe sepsis or septic shock, data are lacking on the subset of patients with SAP, particularly in cases with uninfected necrosis. We treated with HCO-CVVHDF a 59-year-old man admitted to our intensive care unit (ICU) with SAP inducing early-onset cardiovascular, respiratory and renal dysfunctions associated with high circulating levels of IL-6 and TNF-α and without overt clinical or laboratory signs of infection. During the treatment, cardiovascular, respiratory and renal functions rapidly normalized and circulating levels of IL-6 and TNF-α consistently decreased. The patient was discharged from ICU on day 20.

Purpose Multidrug-resistant Acinetobacter baumannii (MRAB) is an emerging cause of intensive care unit (ICU) outbreaks. Patients are the main reservoirs, inducing cross transmission. We describe an MRAB outbreak that occurred in the Prato Hospital ICU in June to August 2009. Materials and Methods The ICU consists of 2 separated 4-bed rooms (rooms A and B). The MRAB-positive patients were included in our study. During the outbreak, infection control measures were enhanced; patients and environmental screenings were performed. A 6-month follow-up was carried out. Results Four of 26 patients admitted during the outbreak were MRAB positive. All patients were located in room A; no case was detected in room B either in the hospital or during the follow-up. Management included closure to new admissions, reinforcement of infection control measures, patient and environmental screenings, discharge of room B MRAB-negative patients for at least 5 days after the first case identification. All isolates were carbapenems resistant and tigecycline and colistin susceptible. All patients received tigecycline: 2 were successfully treated, 1 died because of preexisting illness, and 1 developed resistance and recovered after colistin therapy. Conclusions Enhanced infection control measures and adequate antibiotic strategy limited the outbreak. Tigecycline allowed rapid recovery. Nevertheless, resistance ensued; so colistin remained the only therapeutic option. However, pan-drug resistance has been reported.

Over the last 5 y, clinical trials investigating products, procedures, and treatments aimed at preventing infections in the intensive care unit have been described. The findings of these studies appear to confirm the effectiveness of certain preventive procedures. With regard to ventilator-associated pneumonia, the efficacies of decontamination of the oral cavity, continuous suction of subglottic secretions, positioning of the patient, selective decontamination of the digestive tract, and (for higher-risk patients) endotracheal tubes coated with silver, have been demonstrated. Medicated catheters and chlorhexidine-based dressings have been found useful for catheter-related bloodstream infections, and medical catheters have also been shown to be efficacious against urinary tract infections. All these procedures can be incorporated into departmental protocols for the prevention of nosocomial infections in the intensive care unit.

Summary The progressive opening up of Intensive Care Units (ICUs) has brought about a series of questions regarding the presence of relatives alongside patients in intensive care, also for extended periods of time. The presence of visitors in the ward would appear to exacerbate the situation, while at the same time opening up communicative, relational and ethical issues regarding the experience of critical illness, as lived by patients, families or health care professionals (HCPs). Due to the opening up of ICUs, it seemed necessary to take into greater consideration the access of minors in particular, whether infants, children or adolescents. The reason for this particular interest lies in the fact that minors are relatives of a various degree from that of the hospitalised patient. The access of minors in ICUs appears to be an aspect that should not be neglected, but should instead be managed with great care when suggested and planned by the ward staff. Following these observations, an operational protocol was written, which could determine the access of minors and then guide them with the family and HCPs through the various phases of their visits to ICUs. The execution of the procedure also proved to stimulate more in-depth training and greater professionalism on the part of the HCPs and provided them with practical guidance, thus resolving their previous sensations of unease and of being ill-prepared with respect to conducting a minor through the experience of illness.

Background: We report here a case of a woman affected by fever, weight loss, splenomegaly, and leucopenia associated with trombocytopenia, transferred to the intensive care unit with acute kidney injury and septic shock. Methods: Patient was treated with high cut-off continuous veno-venous hemodialysis (HCO-CVVHD). Results: During treatment, the patient experienced a stable improvement in the hemodynamic, pulmonary function and tissue perfusion parameters. After 48 h of treatment, significant reductions in SOFA score (from 12, before starting the procedure, to 6) and in serum inflammatory mediators (as IL-6, from 599-568 pg/ml) were observed. Leishmania infection was identified as responsible of the septic condition only 48 h after removing hemodialysis. Antiprotozoal therapy was begun and the patient discharged. Conclusions: By supporting the renal function and reducing systemic inflammation, HCO-CVVHD could be a useful bridge therapy. This procedure allowed the medical team to gain sufficient time to diagnose the type of infection and begin an etiological therapy.

Background Gram-negative bacteria are increasingly responsible for nosocomial infections, including ICU-acquired infections. Due to high virulence, rate of multi-drug resistance and limited availability of new agents, these infections create cumbersome clinical burdens, making it important to reduce the risk of their occurrence. The aim of the study was to assess epidemiology-related factors and outcomes of Gram-negative, ICU-acquired infections in a cohort of medical-surgical patients. Methods A retrospective survey was conducted on all patients admitted to a mixed ICU from January 2012 to December 2013. ‘ICU-acquired infections’ were defined as new infections acquired no less than 48 h after ICU admission. Diagnosis was made according to the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC/NHSN) criteria. Differences across patients who did and did not acquire a Gram-negative infection were tested regarding age, sex, body mass index, medical or surgical admission, cardiovascular comorbidities, chronic obstructive pulmonary disease, diabetes, end-stage renal failure, co-existing tumours and prophylactic anti-fungal treatment. Multivariate analysis was used to assess the independency of these associations. Finally, differences in ICU-mortality, ICU-length of stay and duration of mechanical ventilation were tested across patients with and without new, ICU-acquired, Gram-negative infections. Results Of 494 patients admitted to the ICU, 46 (9.3 %) acquired an infection 48 or more hours after admittance. In 30/46 patients (65.2 %) the isolated bacterium was Gram-negative. Univariate analysis showed that clinical factors associated with new ICU-acquired Gram-negative infections were medical admission (p

Objective: To investigate whether an inflammatory response occurs in patients undergoing infrarenal aortic abdominal aneurysm repair, the localization and timing (ischemia and/or reperfusion) of this activation, and finally whether it affects postoperative pulmonary function. Design: Prospective, observational study. Setting: Academic referral center in Italy. Patients: We included 12 patients undergoing infrarenal aortic abdominal aneurysm repair and 12 patients undergoing major abdominal surgery. Interventions: Timed measurement of gene activation (angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes) in muscle biopsies by reverse transcriptase-polymerase chain reaction (RT-PCR), and prospective assessment of interleukin-6 plasma concentration and pulmonary function (Pao 2 /Fio 2 and Pao 2 /PAo 2 ratios). Measurements and Main Results: After 30 mins of aortic clamping, angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes were all over-expressed at RT-PCR studies in quadriceps muscle of patients undergoing aortic abdominal aneurysm repair, and the overex-pression persisted after reperfusion. In situ hybridization and immunohistochemistry revealed that the inflammatory response was localized in endothelial cells. A significant increase in plasma interleukin-6 concentrations was then detectable at 6 and 12 hrs after reperfusion in aortic abdominal aneurysm surgery compared with patients undergoing abdominal surgery (p

During the last decade, blood purification therapies have been proposed as an effective therapy to control the cytokines dysregulation in systemic inflammatory syndromes. Among them, the treatment with high cut-off membranes is characterized by larger pore size and more effective clearance for middle molecular weight molecules (cytokines). In this paper, we performed a thoughtful review of the literature on HCO being used for blood purification indications in all systemic inflammation syndromes. Clinical and experimental studies show that the use of high effluent flows in a pure diffusive treatment effectively removes serum cytokines with a safe profile in albumin clearance. In clinical studies, the removal of these inflammatory mediators is associated with a significant improvement in hemodynamic condition, oxygenation indices, and organ dysfunction. © 2014 S. Karger AG, Basel

Invasive aspergillosis has been mainly reported among immunocompromised patients during prolonged periods of neutropenia. Recently, however, non-neutropenic patients in the ICU population have shown an increasing risk profile for aspergillosis. Associations with chronic obstructive pulmonary disease and corticosteroid therapy have been frequently documented in this cohort. Difficulties in achieving a timely diagnosis of aspergillosis in non-neutropenic patients is related to the non-specificity of symptoms and to lower yields with microbiological tests compared to neutropenic patients. Since high mortality rates are typical of invasive aspergillosis in critically ill patients, a high level of suspicion and prompt initiation of adequate antifungal treatment are mandatory. Epidemiology, risk factors, diagnostic algorithms, and different approaches in antifungal therapy for invasive aspergillosis in non-neutropenic patients are reviewed.

Purpose Totally implantable venous access devices (Ports) represent the mainstay for infusion therapy in patients undergoing chemotherapy, total parenteral nutrition and/or long-term antibiotic treatment. Amongst mechanical complications, lesions of the catheter wall represent a rare but potentially severe condition. We report our experience with the accidental detection of catheter ruptures in a series of ports removed for complication or for end of use. Methods All ports removed from January 2011 to June 2013 were considered. All removed ports had been inserted according to a standardized protocol including ultrasound-guided percutaneous venipuncture (out-of-plane or in-plane approaches) and electrocardiogram-guided positioning of the tip. Once removed, each catheter was checked by inspection and saline instillation in order to evaluate the integrity of the device itself and rule out possible ruptures. Results In over 338 removed ports, 12 Groshong catheters out of 65 (18.5%) had evidence of partial rupture of the catheter wall. Amongst considered variables, “out-of-plane” approach and type of port (silicon, closed tip with Groshong valve) were the only ones significantly associated with catheter ruptures (p=0.0003 and 0.0008, respectively). We could detect no evidence of rupture in any silicon open-ended catheter (Celsite ports) or in any catheter inserted by “in-plane” approach to the vein. Conclusions The actual advantage of using port connected with Groshong silicon catheters should be questioned, since apparently they are more fragile than standard catheters. Furthermore, ultrasound-guided “out-of-plane” puncture of the internal jugular vein should be discouraged.

Summary The famous military leader Giovanni de' Medici died in 1526, during a battle against the Emperor army. He was wounded in his right thigh and died after the surgical intervention, which was performed by Magister Abraham. His friends suspected that the surgeon had "poisoned" his instruments, but someone wrote that Magister Abraham had purposely left "too much wounded flesh". After five centuries it is now possible to confirm this rumour.

Objective To compare the FloTrac/Vigileo TM cardiac output (CO FT/V ) and the MostCare ® /PRAM cardiac output (CO MC/P ) versus transthoracic echocardiographic cardiac output estimation (reference method; CO ECHO ). Design Prospective observational study. Setting Single center, Cardio-Thoracic and Vascular Surgery/Intensive Care Unit. Participants Patients undergoing elective vascular surgery. Interventions Cardiac output measurement with two pulse contour methods: the FloTrac/Vigileo TM and the MostCare ® /PRAM before (T1) and after (T2) fluid loading versus echocardiography (reference method). Measurements and Main Results One hundred fifty-six CO measurements were performed in 26 patients. The data showed poor agreement between CO ECHO and CO FT/V : r 2 = 0.29 (T1) and 0.27 (T2); bias −0.37 (T1) and −0.40 (T2) L/min; limits of agreement from −3.10 to 2.42 (T1) and from −3.0 to 2.2 (T2) L/min. The percentage error was 51.7% (T1) and 49.3% (T2). Conversely, CO MC/P resulted in agreement with echocardiography: r 2 = 0.76 (T1) and 0.80 (T2); bias −0.01 (T1) and −0.06 (T2) L/min; limits of agreement from −1.13 to 1.11 (T1) and from −0.90 to 0.80 (T2) L/min, with a PE of 22.4% (T1) and of 17.0% (T2). Conclusions In patients undergoing vascular surgery, the FloTrac/Vigileo TM did not demonstrate that it was a reliable system for CO monitoring when compared with echocardiography-derived CO. However, MostCare ® /PRAM was shown to estimate CO with a good level of agreement with echocardiographic measures.

Introduction The kidneys play a crucial role in the regulation of electrolytes and acid-base homeostasis. Urinary Strong Ion Difference (SIDu = NaU + KU—ClU) represents an important aspect of renal acid-base regulation. We evaluated the role of SIDu as a marker of renal dysfunction in critically ill patients. Materials and Methods Patients admitted to the Medical Intensive Care Unit with a diagnosis of AKI for whom concomitant urinary samples available for SIDu calculation were retrospectively reviewed and staged according to KDIGO criteria for 3 days from inclusion. Patients were classified as Recovered (R-AKI) or Persistent-AKI (P-AKI) whether they exited KDIGO criteria within the 3-day observation period or not. A control group with normal renal function and normal serum acid-base and electrolytes was prospectively recruited in order to identify reference SIDu values. Results One-hundred-and-forty-three patients with a diagnosis of AKI were included: 77 with R-AKI, and 66 with P-AKI. Thirty-six controls were recruited. Patients with P-AKI had more severe renal dysfunction and higher mortality than patients with R-AKI (SCr 2.23(IQR:1.68–3.45) and 1.81(IQR1.5–2.5) mg/dl respectively, p

For an UltraSound guided Infraclavicular Block, a non-inferiority randomized study was conducted comparing two volumes of ropivacaine 0.75%: 35 ml vs 30ml. Fifty 18-70 years old patients undergoing upper limb surgery, ASA I-II were enrolled. Exclusion criteria included existing neurologic disease, coagulopathy, allergy, pregnancy, previous surgery in clavicular region, BMI more than 30 kg/m2 or patients unable to give written consent. Using US guidance, a 22 gauge/80 mm SonoPlex needle (Pajunk®) was advanced until the tip was located dorsally to the artery at a 6-o’clock position. Correct placement was ensuring by a “double bubble” sign. The block was performed by delivering ropivacaine 0.75% via an infusion pump (Alaris® PK) at 600 ml/h.

Since the initial use of prosthetic heart valves, the use of cardiac prosthesis and implantable devices has revolutionized the therapeutic options available to patients (de Oliveira et al.,2009). Cardiac Permanent PaceMakers (PPMs) have been implanted since the early 1960s. Over the past 50 years there have been tremendous advances in both the design of the device and the software employed. In the mid 1960s, transvenous leads were developed that could be inserted through a vein and thence into the heart, thus preventing the need for a thoracotomy. The development of ‘active fixation’ leads ensured a better contact with the endocardium and the presence of a steroid eluting tip helped to reduce any inflammation that might result. The introduction of the lithium iodine battery has dramatically increased the battery life to well over ten years. Radiofrequency programming became available in the 1970s, allowing simple adjustments to be made to pacemaker’s settings without the need for surgery. Today, permanent pacemakers and ICD (Implantable Cardiac Defibrillator), together with any adjustments, can be completed within minutes using a portable computer. Information regarding events such as periods of bradycardia, tachycardia or ventricular fibrillation can be stored within the memory of the device and accessed by the specialist during the routine checkup. To maintain atrio-ventricular synchrony, dual chamber pacing was then introduced. Moreover, in the late 1990s, pacemaker technology had improved to the extent that it became possible to increase the pacing rate to match the patient’s activity level (Allen et al., 2007). A wide range of cardiac implantable electronic devices (CIEDs) are now available, including ICDs and cardiac resynchronization systems. PPMs are commonly used in patients with atrioventricular conduction block, sick sinus syndrome, and symptomatic sinus bradycardia, whereas ICDs target primarily patients at risk for life-threatening ventricular arrhythmias. Since clinical trials have consistently demonstrated the ability of the ICD to reduce mortality in selected patients with moderate-to-severe left ventricular systolic

Treatment with analgesics before surgery may be effective in reducing post-operative pain. This approach is defined as "pre-emptive analgesia" and recent reviews show conflicting results.The aim of this study was to investigate the efficacy of pre-emptive analgesia with sublingual morphine sulphate, compared with sublingual midazolam in patients undergoing elective abdominal surgery.Prior to surgery, 29 patients were randomized and premedicated with sublingual morphine sulphate 0.5 mg/kg (Group A; n = 15) or with sublingual midazolam 0.03 mg/kg (Group B; n = 14). General anaesthesia was maintained with sevoflurane and fentanyl. Post-operatively, intravenous (IV) acetaminophen 0.02 mg/kg was given to all patients and a bolus of IV morphine 0.1 mg/kg was given to Group B patients. Post-operative pain was controlled by IV morphine via a patient-controlled analgesia (PCA) device. IV acetaminophen 0.02 mg/kg was also administered four times daily. Efficacy was assessed using static Visual Analogue Scale (sVAS) scores, dynamic VAS (dVAS) scores, number of PCA doses administered and number of failed doses registered from the PCA device at 4, 6, 24 and 48 hours after surgery. Results were statistically analysed using the Student t-test; a value of p0.05 was considered significant.Significantly lower sVAS and dVAS scores were observed in Group A patients than in Group B at all assessment periods (p0.05 for all time points). There were less PCA administered and failed doses in Group A, compared with Group B (all time points p0.05). There was no difference in the occurrence of common side effects between the two treatments.In patients undergoing elective abdominal surgery, premedication with sublingual morphine sulphate results in a better control of post-operative pain, compared to premedication with sublingual midazolam. The beneficial effect of pre-operative sublingual morphine sulphate was apparent in the immediate post-operative period and was sustained over the 48-hour assessment period.

CONTEXT: The benefit of corticosteroids in severe sepsis and septic shock remains controversial. OBJECTIVE: We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. DATA SOURCES: We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. STUDY SELECTION: Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. DATA EXTRACTION: All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. RESULTS: We identified 17 randomized trials (n = 2138) and 3 quasi-randomized trials (n = 246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P = .05; I(2) = 53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P = .83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P = .02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P = .02; I(2) = 4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, -7.04 to -1.94; P < .001; I(2) = 0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P = .50; I(2) = 0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P = .92; I(2) = 8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P = .58; I(2) = 30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P < .001; I(2) = 0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P < .001; I(2) = 0%). CONCLUSIONS: Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.

Critically ill patients, not infrequently present alterations of physiological parameters that determine the success/failure of therapeutic interventions as well as the final outcome. Sepsis and polytrauma are two of the most common and complex syndromes occurring in Intensive Care Unit (ICU) and affect drug absorption, disposition, metabolism and elimination. Pharmacological management of ICU patients requires consideration of the unique pharmacokinetics associated with these clinical conditions and the likely occurrence of drug interaction. Rational adjustment in drug choice and dosing contributes to the appropriateness of treatment of those patients.

The aim of this study was to investigate the effect of low-dose hydrocortisone on glomerular permeability measured by the microalbuminuria to creatinine ratio (MACR) and on other markers of sepsis in severe septic patients.Randomized prospective study.University intensive care unit.The study involved 40 patients with severe sepsis randomized into the hydrocortisone group (n = 20) and the standard therapy group (n = 20).The hydrocortisone group received standard therapy plus a continuous infusion of hydrocortisone for 6 days, whereas the standard therapy group received only standard therapy.MACR, serum C-reactive protein, and procalcitonin concentrations were recorded every day from the day before the steroid therapy (T(0)) until the 6 days after (T(1), T(2), T(3), T(4), T(5), and T(6)). Concentrations in the hydrocortisone group and the standard therapy group were compared using Mann-Whitney test at each time. We also compared with Wilcoxon signed rank test the values determined in each group at T(0) with those at each subsequent time. Median MACR decreased from T(0) to T(6) in both patient groups; however, values were significantly lower in the hydrocortisone group from T(3) through to T(6). Median serum C-reactive protein also decreased from T(0) in both patient groups, with significantly lower values in the hydrocortisone group from T(3) through to T(6). There were no significant differences in procalcitonin between groups compared with baseline values or at any individual time point.Low-dose hydrocortisone seems to reduce MACR and serum C-reactive protein but not procalcitonin in patients with severe sepsis. Further studies are needed to confirm these results and to understand the underlying molecular mechanisms.